Thyroid cancer is the most common endocrine malignancy. With a rapidly rising incidence in recent years, novel efficient management strategies are increasingly needed for this cancer. Remarkable advances have occurred in understanding several major biologic areas of thyroid cancer, including the molecular alterations for the loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations, and the aberrant methylation of functionally important genes in thyroid tumorigenesis and pathogenesis. These exciting advances provide unprecedented opportunities for the development of molecular-based novel diagnostic, prognostic, and therapeutic strategies for thyroid cancer.